Fernandes Juliane C R, Gonçalves André N A, Floeter-Winter Lucile M, Nakaya Helder I, Muxel Sandra M
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Instituto de Medicina Tropical da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Front Genet. 2023 Jan 4;13:1051568. doi: 10.3389/fgene.2022.1051568. eCollection 2022.
It is well established that infection with alters the host cell's transcriptome. Since mammalian cells have multiple mechanisms to control gene expression, different molecules, such as noncoding RNAs, can be involved in this process. MicroRNAs have been extensively studied upon infection, but whether long noncoding RNAs (lncRNAs) are also altered in macrophages is still unexplored. We performed RNA-seq from THP-1-derived macrophages infected with (), () and () investigating a previously unappreciated fraction of macrophage transcriptome. We found that more than 24% of the total annotated transcripts and 30% of differentially expressed (DE) RNAs in -infected macrophage correspond to lncRNAs. LncRNAs and protein coding RNAs with altered expression are similar among macrophages infected with the species. Still, some species-specific alterations could occur due to distinct pathophysiology in which infection led to a more significant number of exclusively DE RNAs. The most represented classes among DE lncRNAs were intergenic and antisense lncRNAs. We also found enrichment for immune response-related pathways in the DE protein coding RNAs, as well as putative targets of the lncRNAs. We performed a coexpression analysis to explore potential cis regulation of coding and antisense noncoding transcripts. We identified that antisense lncRNAs are similarly regulated as its neighbor protein coding genes, such as the BAALC/BAALC-AS1, BAALC/BAALC-AS2, HIF1A/HIF1A-AS1, HIF1A/HIF1A-AS3 and IRF1/IRF1-AS1 pairs, which can occur as a species-specific modulation. These findings are a novelty in the field because, to date, no study has focused on analyzing lncRNAs in -infected macrophage. Our results suggest that lncRNAs may account for a novel mechanism by which can control macrophage function. Further research must validate putative lncRNA targets and provide additional prospects in lncRNA function during infection.
众所周知,感染[病原体名称未给出]会改变宿主细胞的转录组。由于哺乳动物细胞具有多种控制基因表达的机制,不同分子,如非编码RNA,可能参与这一过程。微小RNA在[病原体名称未给出]感染后已得到广泛研究,但巨噬细胞中的长链非编码RNA(lncRNA)是否也会发生改变仍未被探索。我们对源自THP-1的巨噬细胞进行RNA测序,这些巨噬细胞分别感染了[病原体名称未给出1]、[病原体名称未给出2]和[病原体名称未给出3],以研究巨噬细胞转录组中一个此前未被重视的部分。我们发现,在感染[病原体名称未给出]的巨噬细胞中,超过24%的总注释转录本和30%的差异表达(DE)RNA对应于lncRNA。在感染不同[病原体名称未给出]物种的巨噬细胞中,表达发生改变的lncRNA和蛋白质编码RNA相似。然而,由于不同的病理生理学,某些物种特异性改变可能会发生,其中[病原体名称未给出]感染导致了更多数量的仅差异表达的RNA。差异表达lncRNA中最主要的类别是基因间lncRNA和反义lncRNA。我们还发现差异表达蛋白质编码RNA以及lncRNA的假定靶标中存在免疫反应相关途径的富集。我们进行了共表达分析以探索编码和反义非编码转录本的潜在顺式调控。我们发现反义lncRNA与其相邻的蛋白质编码基因受到类似调控,如BAALC/BAALC-AS1、BAALC/BAALC-AS2、HIF1A/HIF1A-AS1、HIF1A/HIF1A-AS3和IRF1/IRF1-AS1对,这可能作为一种物种特异性调控发生。这些发现是该领域的新进展,因为迄今为止,尚无研究专注于分析感染[病原体名称未给出]的巨噬细胞中的lncRNA。我们的结果表明,lncRNA可能是[病原体名称未给出]控制巨噬细胞功能的一种新机制。进一步的研究必须验证假定的lncRNA靶标,并为[病原体名称未给出]感染期间lncRNA的功能提供更多前景。
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